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Isopenicillin N synthase (IPNS) catalyzes the unique reaction of l-δ-(α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) with dioxygen giving isopenicillin N (IPN), the precursor of all natural penicillins and cephalosporins. X-ray free-electron laser studies including time-resolved crystallography and emission spectroscopy reveal how reaction of IPNS:Fe(II):ACV with dioxygen to yield an Fe(III) superoxide causes differences in active site volume and unexpected conformational changes that propagate to structurally remote regions. Combined with solution studies, the results reveal the importance of protein dynamics in regulating intermediate conformations during conversion of ACV to IPN. The results have implications for catalysis by multiple IPNS-related oxygenases, including those involved in the human hypoxic response, and highlight the power of serial femtosecond crystallography to provide insight into long-range enzyme dynamics during reactions presently impossible for nonprotein catalysts.

RUL (remaining useful life) estimation is one of the main functions of the predictive analytics systems for rotary machines. Data-driven models based on large amounts of multisensory measurements data are usually utilized for this purpose. The use of adjustable bearings, on the one hand, improves a machine's performance. On the other hand, it requires considering the additional variability in the bearing parameters in order to obtain adequate RUL estimates. The present study proposes a hybrid approach to such prediction models involving the joint use of physics-based models of adjustable bearings and data-driven models for fast on-line prediction of their parameters. The approach provides a rather simple way of considering the variability of the properties caused by the control systems. It has been tested on highly loaded locomotive traction motor axle bearings for consideration and prediction of their wear and RUL. The proposed adjustable design of the bearings includes temperature control, resulting in an increase in their expected service life. The initial study of the system was implemented with a physics-based model using Archard's law and Reynolds equation and considering load and thermal factors for wear rate calculation. The dataset generated by this model is used to train an ANN for high-speed on-line bearing RUL and wear prediction. The results show good qualitative and quantitative agreement with the statistics of operation of traction motor axle bearings. A number of recommendations for further improving the quality of predicting the parameters of active bearings are also made as a summary of the work. [ABSTRACT FROM AUTHOR]

The paper considers introduction of automated and robotic means in the construction industry, in particular for building from block materials, and its possible impact at improvement of building process quality and reliability of buildings and structures. Currently, manual labor is used for most operations during the block-laying process. Unstable quality of manual labor causes numerous defects that are detected during the technical inspection and monitoring of buildings and structures. Simultaneously, the current technological level is enough high for developing automated and robotic means for main operations in the considered process. At the same time there is the issue of ensuring the quality of the operations performed by such devices. The most significant limiting factor is measurement means, like sensors and algorithms used for processing the data obtained from the sensors. Thus, the basic requirements to the measurement means based on the current standards have been formulated during this research. Applying the automated and robotic means meeting these requirements will allow improve the block-laying process qualitatively, both in terms of its performance and in terms of reliability of the resulting constructions.

The problem of rotor machines modification requires development of new approaches to the design of specific nodes. As bearings are considered the most important elements of rotor machines, such approaches can imply the application of active control. In the present paper using the example of fluid-film bearings the approach is considered to enchancing energy efficiency of rotor machines by means of generating optimal trajectories. Means are shown to analyze the dynamics of a rotor system and types of the obtained trajectories. The paper also covers the approach to setting the criteria of energy efficiency of rotor’s trajectories. After the optimal trajectory is obtained, active bearings are proved feasible to control the displacement of a rotor by generating a force to match the actual trajectory to the calculated one, and by this to decrease the energy loss.

Na+/H+ exchangers (NHEs) are ancient membrane‐bound nanomachines that work to regulate intracellular pH, sodium levels and cell volume. NHE activities contribute to the control of the cell cycle, cell proliferation, cell migration and vesicle trafficking. NHE dysfunction has been linked to many diseases, and they are targets of pharmaceutical drugs. Despite their fundamental importance to cell homeostasis and human physiology, structural information for the mammalian NHE was lacking. Here, we report the cryogenic electron microscopy structure of NHE isoform 9 (SLC9A9) from Equus caballus at 3.2 Å resolution, an endosomal isoform highly expressed in the brain and associated with autism spectrum (ASD) and attention deficit hyperactivity (ADHD) disorders. Despite low sequence identity, the NHE9 architecture and ion‐binding site are remarkably similar to distantly related bacterial Na+/H+ antiporters with 13 transmembrane segments. Collectively, we reveal the conserved architecture of the NHE ion‐binding site, their elevator‐like structural transitions, the functional implications of autism disease mutations and the role of phosphoinositide lipids to promote homodimerization that, together, have important physiological ramifications. SYNOPSIS: Exchange of sodium for protons across cell membranes regulates intracellular pH and cell volume. Here, cryo‐EM combined with functional assays provides first insights into the structure and membrane context of a mammalian Na+/H+ exchanger (NHE). The Equus caballus NHE9/SLC9A9 monomer comprises 13 transmembrane segments and forms a homodimer with similar topology as bacterial antiporter homologues.The NHE9 structure at 3.2 Å shows an inward‐facing conformation, with a highly conserved Na+‐binding site.Functional assays suggest stabilization of the NHE9 homodimer by phosphoinositide lipid binding to an extracellular loop domain.Autism‐associated disease mutants map onto highly flexible regions in NHE9, likely impairing endosomal pH regulation by NHE9.Intrinsic NHE9 dynamics support an elevator‐like alternating access mechanism in mammalian Na+/H+ exchange. [ABSTRACT FROM AUTHOR]

The paper describes the approach to building the algorithm for controlling the rotor motion in a hybrid mechatronic bearing. Such bearings include a rolling bearing, a gas foil bearing, an electromagnetic and a piezo actuator. Fuzzy logic techniques are used in the proposed algorithm. Its main aim is to minimize the deviation of the rotor position in the bearing from the equilibrium position. It results in reducing the vibrational activity of the rotor-bearing system and reducing the friction losses. [ABSTRACT FROM AUTHOR]

Membrane protein purification by means of detergents is key to isolating membrane-bound therapeutic targets. The role of the detergent structure in this process, however, is not well understood. Detergents are optimized empirically, leading to failed preparations, and thereby raising costs. Here we evaluate the utility of the hydrophilic-lipophilic balance (HLB) concept, which was introduced by Griffin in 1949, for guiding the optimization of the hydrophobic tail in first-generation, dendritic oligoglycerol detergents ([G1] OGDs). Our findings deliver qualitative HLB guidelines for rationalizing the optimization of detergents. Moreover, [G1] OGDs exhibit strongly delipidating properties, regardless of the structure of the hydrophobic tail, which delivers a methodological enabling step for investigating binding strengths of endogenous lipids and their role for membrane protein oligomerization. Our findings will facilitate the analysis of challenging drug targets in the future., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)